cover cover title: author: publisher: isbn10 | asin: print isbn13: ebook isbn13: language: subject publication date: lcc: ddc: subject: next page > Biochemistry : A Short Course Matthews, Harry Roy.; Freedland, Richard A.; Miesfeld, Roger L John Wiley & Sons, Inc (US) 0471022055 9780471022053 9780585329482 English Biochemistry 1997 QP514.2.M387 1997eb 574.19/2 Biochemistry cover next page > file:///C:/ ents%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/cover.html[12/10/2009 10:11:17] page_iii < previous page page_iii next page > Page iii Biochemistry A Short Course Harry R Matthews Department of Biological Chemistry University of California School of Medicine Davis, California Richard A Freedland Department of Molecular Biosciences University of California School of Veterinary Medicine Davis, California Roger L Miesfeld Department of Biochemistry University of Arizona Tucson, Arizona < previous page page_iii next page > file:///C:/ ts%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_iii.html[12/10/2009 10:11:20] page_iv < previous page page_iv next page > Page iv Address all Inquiries to the Publisher Wiley-Liss, Inc., 605 Third Avenue, New York, NY 10158-0012 Copyright © 1997 by Wiley-Liss, Inc Printed in the United States of America The text of this book is printed on acid-free paper Under the conditions stated below the owner of copyright for this book hereby grants permission to users to make photocopy reproductions of any part or all of its contents for personal or internal organizational use, or for personal or internal use of specific clients This consent is given on the condition that the copier pay the stated per-copy fee through the Copyright Clearance Center, Incorporated, 27 Congress Street, Salem, MA 01970, as listed in the most current issue of "Permissions to Photocopy" (Publisher's Fee List, distributed by CCC, Inc.), for copying beyond that permitted by sections 107 or 108 of the US Copyright Law This consent does not extend to other kinds of copying, such as copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale Library of Congress Cataloging-in-Publication Data Matthews, Harry Roy, 1942Biochemistry: a short course / Harry R Matthews, Richard A Freedland, Roger L Miesfeld p cm Includes Index ISBN 0-471-02205-5 (pbk.: alk paper) Biochemistry I Freedland, Richard A (Richard Allan) II Miesfeld, Roger L III Title QP514.2.M387 1996 574.19'2dc20 96-16469 Printed in the United States of America 10 < previous page page_iv next page > file:///C:/ ts%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_iv.html[12/10/2009 10:11:21] page_v < previous page page_v next page > Page v This book is dedicated to our wives, Iris, Beverly, and Elizabeth, for their patience and support during all the evenings and weekends we spent working on this project < previous page page_v next page > file:///C:/ ts%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_v.html[12/10/2009 10:11:21] page_vii < previous page page_vii next page > Page vii Contents Preface xv Acknowledgments xvi Chapter 1: Molecules and Cells Introduction Molecules and Cells Subcellular Structure Supracellular Structure Cellular Processes Need Energy Supplied by ATP Forces between Molecules Summary References Review Question Answer to Review Question Chapter 2: Nucleic Acids Introduction Structure file:///C:/ s%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_vii.html[12/10/2009 10:11:22] page_vii Chemical (Primary) Structure of DNA and RNA Nucleic Acid Secondary Structure 13 Nucleic Acid Tertiary Structure 13 Domains and Supercoiling 15 DNA Denaturation 15 Reassociation 17 Hybridization 19 Nucleic Acid Sequencing 19 DNA Sequencing by Sanger's Method 22 Summary 23 References 23 Review Questions 23 Answers to Review Questions Chapter 3: Proteins 25 Introduction 25 Amino Acids 25 Electrostatic Properties file:///C:/ s%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_vii.html[12/10/2009 10:11:22] page_vii 27 Hydrophobicity 28 Chemical Reactivity 28 Polypeptides 30 Protein Structure 32 Secondary Structure 35 Functional Motifs and Domains 35 Structural Domains 36 Tertiary Structures 37 Quaternary Structures 37 Posttranslational Modifications 38 Protein Purification 38 Column Chromatography 39 Gel Electrophoresis of Proteins 40 Summary 40 Text Box: Definition of pK and pI 41 Text Box: Forces Involved in Determining Protein Structure file:///C:/ s%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_vii.html[12/10/2009 10:11:22] page_vii < previous page page_vii next page > file:///C:/ s%20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_vii.html[12/10/2009 10:11:22] page_viii < previous page page_viii next page > Page viii 42 A Worked Example Using the Henderson-Hasselbalch Equation 42 References 42 Review Questions 43 Answers to Review Questions Chapter 4: Membranes 45 Introduction 45 Lipids, Phospholipids, and Membrane Structure 49 Proteins in Membranes 51 Membrane Transport Proteins 52 Membrane-Bound Receptors and Other Intracellular Signaling Molecules 54 Summary 54 References 55 Review Questions 55 Answers to Review Questions Chapter 5: Nucleoprotein Complexes 57 Introduction file:///C:/ %20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_viii.html[12/10/2009 10:11:23] page_viii 57 Chromosomes 58 Chromatin 58 Chromosomal Proteins 60 Nucleosomes 60 Higher-Order Chromatin Structures 61 Structure of Active Chromatin 62 Sequence-Specific DNA-Binding Proteins 63 Ribonucleoprotein Complexes 63 Nuclear Ribonucleoprotein Complexes 63 Ribosomes 64 Signal-Recognition Particles 65 Summary 65 References 65 Review Questions 66 Answers to Review Questions Chapter 6: Hemoglobin Illustrates Protein Behavior 67 Introduction file:///C:/ %20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_viii.html[12/10/2009 10:11:23] page_502 Second Law of Thermodynamics, cellular processes and, 3-4 Second messenger system: defined, 486 phosphorylation cascades, 433-434 plasma membrane and, 52-54 Secretory vesicles, protein targeting, 399 Sedimentation coefficient, ribosomes, 63-64 Self-splicing RNA, overview, 358 Semiconservative DNA replication, 308-309 Semilike forest virus, endocytosis, 442-443 Sequence divergence: defined, 486 eukaryotic gene organization, 296 Sequence-specific protein-DNA interactions, analysis, 352-353 binding proteins, 62-63 Sequence tagged sites (STSs), Y chromosome mapping, 300-301 Serine: < previous page page_502 next page > file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_502.html[12/10/2009 10:18:09] page_503 < previous page page_503 next page > Page 503 membrane structure, 45, 47 metabolism, 244-246 Serine protease: digestive enzymes and, 117 factor Xa, as, 120-121 Serotonin, 264-266 SH2 protein, ras oncogene and, 470-471 Shine-Dalgarno sequence, polypeptide synthesis, 384-387 Short interspersed elements (SINEs), repetitive DNA sequences, 247-298 Sialic acid, glycolipid structure, 45-46 Sickle cell trait: bisphosphoglycerate and, 75 hemoglobin genetics, 67 Hemoglobin S (HbS) and, 79 Sigmoidal kinetics: allosteric enzymes, 112-113 metabolism, 140-141 phosphofructokinase metabolism, 143-144 sigmoidal curve, 486 Signal patch, protein targeting, 395-397 Signal peptides: defined, 486 protein targeting, 395-397 mitochondrial signal peptide, 397-398 Signal recognition particle (SRP): protein targeting, 398 structure and function, 64, 486 Signal transduction: defined, 486 hormone receptors, 213-214 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_503 protein phosphorylation, 37-38 second messenger systems, 54 Single-strand binding protein (SSB), replication fork, 314-315 Site-directed mutagenesis, Kunkel strategy, 351-353 Site-specific recombination: DNA and, 330-331 immunoglobulin genes, 334 Skeletal muscle, calcium (Ca2+) and, 133-134 Skin cancer, oncogenes, 460-461 Small nuclear ribonucleoproteins (snRNPs): defined, 486 ribonucleoprotein complexes, 63 RNA splicing, 361-362 Small nuclear RNA (snRNA): RNA splicing, 361-362 RNA synthesis and, 341 Smallpox virus, structure, 446 Small t antigen, SV40 virus and, 448 Smoking, hemoglobin function, 67 SNF/SWI nuclear proteins, eukaryotic gene expression, 435 Solenoid, chromatin structure, 61 Solute molecules, hydrophilic and hydrophobic molecules, 27-28 Somatic cells: chromosomes, 57 defined, 486 genetics and, 477 human genome and, 293 mutations, cancer and, 459-460 Southern blotting: defined, 486 DNA hybridization, 17, 19-20 Specificity, enzyme regulation, metabolic pathways, 109 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_503 Sphingomyelin, structure, 45-46 Spliceosomes: defined, 486 hnRNA splicing, 358 STAT transcription factors, phosphorylation cascade, 435-436 Steric hindrance: defined, 41 hydrogen bonding, Steroid hormones: extracellular signaling molecules, 52-53 receptors: DNA-heterodimer binding, 429-432 heterodimer function, 427-429 transcriptional control, 427-432 structure and function, 216, 218 Streptomycin, protein synthesis inhibition, 391 Structural domains, protein, 35-36 Subcellular structure, 2-3 Substrates: defined, 486 enzyme-catalyzed reactions, 87 enzyme regulation of concentration, 102 two-substrate reactions, 92-93 Subtilisin, specificity, 84 Subunit association/dissociation, enzyme regulation, 102 Succinate dehydrogenase, citric-acid cycle, 154 Succinylcholine: enzyme inhibitors, 106-107 membrane transport, 52 Succinyl CoA synthetase, citric-acid cycle, 154 Sugar, cellular energy production and, 3-4 Suicide enzyme inhibition, 107-108 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_503 Sulfur amino acids, 250-253 Supercoiling: defined, 486 nucleic acids, 14-15 Supracellular structures, SV40 virus: DNA replication and cell transformation, 447-448 structure, 446-449 Svedberg units, ribosomal RNA (rRNA) processing, 364-365 Symport, carrier proteins, 51 Synapses, membrane transport proteins, 52 T T4 DNA polymerase, 320 Tandem array, eukaryotic gene organization, 297 Tandem repeat See also Direct repeats defined, 486 T antigens, SV40 virus and, 448-449 Taq polymerase, 320, 486 Target cells, extracellular signaling molecules, 52-53 Targeted gene transfer, homologous recombination, 335-336 TATA binding protein (TBP): eukaryotic gene expression, 423-424 transcription initiation, 349-353 TATA box, eukaryotic gene promoters, 348-349 Tau proteins, structure and function, 129-130 Taurine, cysteine metabolism, 247 Tax protein, retroviruses and, 453 TBP-associated factors (TAFs): eukaryotic gene expression, 423-424 site-directed mutagenesis, 351-353 T-cells, actin filaments, 130-131 Telomeres: file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_503 sequence-specific DNA-binding proteins, 62-63 structure, 293-295 Template strand: defined, 486 RNA synthesis initiation and, 343 -10 region, transcription initiation, 343 Termination: polypeptide synthesis, 389-390 transcription, 345 Tertiary protein structure, 36-37 Tetracycline, protein synthesis inhibition, 391 Tetrahydrofolate: histidine catabolism, 259-260 purine metabolism and IMP formation, 273-274 TFIID/TFIIA complex, RNA pol II initiation, 346 a-Thalassemia, hemoglobins and, 77-78 b-Thalassemia, hemoglobins and, 77-78 Thalassemias, hemoglobin and, 67, 77-78 Thereonine aldolase, threonine metabolism, 246 Thermodynamics, metabolism and, 139-141 Thiamin, structure and function, 97-98 Thiamine pyrophosphate (TPP), structure, 96 Thimidine-kinase gene promoter, eukaryotic genes, 348-349 30-nm fiber, chromosome structure, 58 -35 region, transcription initiation, 343 Threonine, metabolism, 246 Threonine dehydratase, threonine metabolism, 246 Thrombin: specificity, 84 structure and function, 121-123 Thymidine triphosphate (TTP): competitive enzyme inhibition, 103 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_503 synthesis, cancer chemotherapy, 109-111 Thymine: DNA primary structure, 7-8 pyrimidine synthesis and, 280-282 Thymine dimers: DNA damage and, 325, 327 nucleotide excision repair, 328-329 Thyroid receptors (TR), DNA-heterodimer binding, 429-432 Thyroxine, tyrosine catabolism, 262 Tight junctions: cell-cell interactions, 134 defined, 486 integral membrane proteins, 50-51 Tissue factor, coagulation pathway, 119 Tissue-type plasminogen activator (TPA): drug design, plasminogen structure and function, 123-124 Topoisomerases (I and II), replication fork, 314-315 < previous page page_503 next page > file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_503.html[12/10/2009 10:18:12] page_504 < previous page page_504 next page > Page 504 Topological domains: defined, 486 nucleic acids, 14-15 Trace elements, structure and function, 95-100 Trait, defined, 477, 486 Transamination: alanine, 243-244 defined, 486 sequence, 233-234 Transcript, defined, 486 Transcription See also Gene expression CpG dinucleotide methylation and, 435, 437 defined, 486 DNA-dependent RNA polymerases, 341-345 DNA tertiary structure, 13 genome organization, 291-292 initiation: in E coli, 343-344 in eukaryotes, 346-347 prokaryotic gene regulation, 407 TATA binding protein (TBP), 349-353 nucleus and, prokaryotic gene regulation, \11ac\L operon: catabolic gene-activator protein (CAP) regulation, 411-415 control of, 409-410 IPTG derepression of, 410-411 supercoiling and, 15 units: defined, 486 DNA-dependent RNA polymerases, 342 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_504 Transcription factors: ABF1, DNA replication and, 319 chromosomes, 58 defined, 486 eukaryotic gene expression, 423-424 chimeric transcription factors, 425-427 prokaryotic gene regulation, 407-409 Transduction, defined, 486-487 Transesterification of RNA: group I introns, self-splicing mechanisms, 358-360 Transfection techniques, 427 Transferrin receptor (TfR): protein synthesis, 391 RNA degradation, 369-370 Transfer RNA (tRNA): defined, 487 DNA tertiary structure, 13 eukaryotic gene organization, 295-297 processing, 365 protein synthesis: aminoacyl-tRNA synthetases, 382-384 as molecular adaptor, 381-382 overview, 375 RNA synthesis and, 341 splicing mechanisms, 358 Transformed cell lines: defined, 487 oncogenesis and, 463-464 viral research, 442 Transforming protein, SV40 virus and, 448 Transient cotransfection assays, 427-428 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_504 Transition state, defined, 487 Translation See also Protein synthesis defined, 487 genome organization, 291-292 nucleus and, Translational frameshifting, protein synthesis, 381 Translational read-through, polypeptide synthesis, 390 Translocations, chromosomes, 57 Transmembrane proteins: protein targeting, 400 structure, 49-50 Transport mechanisms: glycolysis and, 142-145 membrane transport, 51-52 Treadmilling, actin filaments, 130 Triacylglycerols: activation and beta oxidation, 191-193 hydrolysis, 189-190 structure, 45 synthesis of, 205-208 Tricarboxylic-acid cycle See Citric-acid cycle Triglycerides See Triacylglycerols triiodothyronine, tyrosine catabolism, 262 Trinucleotide repeats, repetitive DNA sequences, 297 5,¢5¢-triphosphate linkage, mRNA cap, 366-367 Triphosphate isomerase, glycolysis, 147 Triple-stranded helices, collagen synthesis, 134 Triplet ribonucleotides, protein synthesis, 377-378 tRNA nucleotidyl transferase, protein synthesis, 381-382 Tropocollagen, collagen synthesis, 134-135 Tropomyosin: calcium (Ca2+) binding and, 133 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_504 defined, 487 in muscle cells, 131 Troponin: calcium (Ca2+) binding and, 133 defined, 487 in muscle cells, 131 Trp repressor protein, prokaryotic gene regulation, 418-420 Trypsin: in digestion, 117 inhibitors, 118-119 specificity, 84 Trypsinogen, structure and function, 118-119 Tryptophan: catabolism, 264-265 hydrophobicity, 27 hydroxylation pathway, 264, 266 nicotinic acid (Niacin) and, 98-99 prokaryotic gene regulation, 418 Tubulin, microtubule structure and function, 127-129 a-Tubulin, microtubule structure and function, 127-129 b-Tubulin, microtubule structure and function, 127-129 Tumorgenic cell lines: defined, 487 oncogenesis and, 464-465 viral research, 442 Tumor-suppressor genes, oncogenesis, 465-469 Turnover numbers, Michaelis-Menten equation, 91 Two-dimensional gel electrophoresis, 40 Tyrosine: catabolism, 261-263 hydrophobicity, 27 phenylalanine conversion, 260-261 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_504 products from, 262-263 Tyrosine kinases: insulin metabolism, 226-227 phosphorylation cascade, 434-435 ras oncogene and, 470-471 Tyrosine phosphorylation, reversible enzyme covalent modification, 124 U Ubiquitin, protein degradation, 402-403 UDP glucose (UDPG): galactose metabolism, 172 glycogen biosynthesis, 164 Ultraviolet radiation: DNA denaturation, 15-16 oncogenes, 460-461 Uncompetitive enzyme inhibition, 103-104, 106, 108 Unidirectional DNA replication, defined, 309 Uniporter proteins, active transport, 51 Up-regulation of enzymes, 101 Uracil, RNA primary structure, 7-8 Urea, nitrogen metabolism, 232 Urea cycle: arginine synthesis and, 236-237 defined, 487 metabolic disease, 236 sequence of, 234-236 Uric acid: nitrogen metabolism, 232 purine metabolism and, 276-278 Uroporphyrinogens, heme metabolism and, 283-284 V V0 reaction rate: competitive enzyme inhibition, 103 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_504 enzyme-catalyzed reactions, 87-89 Van der Waals forces, macromolecular interaction, V-D-J recombination, antibody diversity, 334 Very-low-density lipoproteins (VLDLs): lipotrophic factors, 253-254 synthesis, 206-208 Vimentin filaments, structure and function, 130 Viral envelope, 442 Virions, 487 Viruses: animal viruses, classification, 443-444 cell membrane properties, 442-443 DNA-DNA viruses, 446-449 DNA-RNA viruses, 449-451 immortalized cell line research, 441-442 RNA-DNA viruses, 451-453 RNA-RNA viruses, 444-446 viral-expression vectors, 453-455 Vitamin C, collagen synthesis, 134 Vitamin D receptors (VDR), DNA-heterodimer binding, 429-432 < previous page page_504 next page > file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_504.html[12/10/2009 10:18:14] page_505 < previous page page_505 Page 505 Vitamin K, prothrombin and thrombin, 122-123 Vitamins, structure and function, 95-100, 487 Vmax maximum reaction rate: defined, 487 enzyme assays, 95 enzyme-catalyzed reactions, 88-89 enzyme regulation, 102 maximum velocity and, 91 Michaelis-Menten equation, 89-93 Von Gierke's disease, 165-167 VPg protein, poliovirus translation, 445-446 W Warfarin, prothrombin and thrombin, 122-123 Watson-Crick base pairing, 8-13 Wernicke's encephalopathy, 98 Wobble hypothesis: codon-anticodon base pairing, 378-380 defined, 487 X Xeroderma pigmentosa, nucleotide excision repair, 328-329 X-ray crystallography: defined, 487 nucleic acid tertiary structure, 13 protein primary structure, 31 Y Y chromosome, mapping of, 300-302 Yeast artificial chromosomes (YACs): defined, 487 Human Genome Project and, 299-300 Yeast cells: file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_505.html[12/10/2009 10:18:16] page_505 DNA replication, 318-319 membrane structure, 47, 49 tRNA splicing in, 358 Z Z-DNA: defined, 479 structure, 9-10 Zelweyer syndrome, protein targeting, 398 Zero-time reassociation, 16 Zinc-finger motif: protein structure, 36 sequence-specific DNA-binding proteins, 62-63 steroid hormone receptors, 427-432 Zymogens: blood clotting, 119 coagulation pathways, 119 common pathways, 120-121 defined, 487 in digestion, 117-119 enzyme covalent modification, 103 extrinsic pathways, 119-121 factor X, 120-121 intrinsic pathways, 119-120 plasminogen and plasmin, 123-124 platelets, 119 prothrombin and thrombin, 121-123 < previous page page_505 file:///C:/ 20and%20Settings/Bariski/Desktop/26134 9780471022053 9780585329482 0471022055/files/page_505.html[12/10/2009 10:18:16] ... 1942Biochemistry: a short course / Harry R Matthews, Richard A Freedland, Roger L Miesfeld p cm Includes Index ISBN 0-471-02205-5 (pbk.: alk paper) Biochemistry I Freedland, Richard A (Richard Allan)... copying for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale Library of Congress Cataloging-in-Publication Data Matthews, Harry Roy,...page_iii < previous page page_iii next page > Page iii Biochemistry A Short Course Harry R Matthews Department of Biological Chemistry University of California School of Medicine Davis, California